Structural Transitions at multiple scales are central to signaling events on and within biological membranes and to the function of membrane proteins. Characterizing these processes is the ultimate goal of experimental structural biology. While novel methodologies in structure determination and biophysical measurements of membrane-associated phenomena have significantly advanced our understanding of some aspects, experimental techniques and approaches do not provide the required high spatial and temporal resolutions to describe a complete atomic-level picture for the underlying dynamics. On the computational side, describing the structural changes underlying biological function in lipid bilayers and membrane proteins requires sampling high-dimensional free energy landscapes inaccessible to conventional sampling techniques such as regular molecular dynamics simulations. We have developed novel approaches that, while numerically expensive, have been very efficient to describe large-scale structural transitions using non-equilibrium methods employing system-specific collective variables, and a novel combination of several state-of-the-art sampling techniques, using loosely coupled, multiple-copy MD simulations and fully atomistic representations. I will describe the methodology, remaining challenges, and its application to a number of membrane transporters, in order to characterize inter-conversion between the major functional states, to characterize the free energy profiles associated with these transitions, and more importantly how chemical details such as ion/substrate binding drastically modulate the energy landscape. The results elucidate highly relevant mechanistic details of the function of membrane transporters providing a detailed structural basis for experimentally observed phenomena.

Emad Tajkhorshid is Hastings Endowed Chair in the Biochemistry Department, as well as holds additional appointments across multiple colleges that include Bioengineering, Pharmacology, Biophysics and Quantitative Biology, Computational Science and Engineering, and the Carle-Illinois College of Medicine at the University of Illinois. His extensive training included a Pharm. D. and a Ph.D. in medicinal chemistry at Tehran University. Dr. Tajkhorshid earned a second Ph.D. in molecular biophysics from the University of Heidelberg, before moving to the University of Illinois at Urbana-Champaign, where he did his postdoctoral studies in computational biophysics at the Beckman Institute. He joined the faculty of the Departments of Biochemistry (LAS) and Pharmacology (UI COM) in 2007 and was fast tracked to associate professor with tenure in 2010 and then again to the rank of professor in 2013. His tenure dossier was selected as one of the two top UIUC tenure cases on campus. In 2015, Professor Tajkhorshid was named a University of Illinois Scholar, after being nominated by both UIUC and UIC campuses. In 2016, he was awarded the Faculty Excellence Award from the School of Molecular and Cellular Biology at UIUC. Later that year he was named Endowed Chair in Biochemistry.